7 results on '"Chang, Fan-Chi"'
Search Results
2. The role of angiopoietin-2 in progressive renal fibrosis.
- Author
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Chang FC and Lin SL
- Subjects
- Animals, Fibrosis, Humans, Kidney Diseases pathology, Myofibroblasts physiology, Pericytes physiology, Vascular Endothelial Growth Factor A physiology, Angiopoietin-2 physiology, Kidney pathology, Kidney Diseases metabolism
- Published
- 2013
- Full Text
- View/download PDF
3. Transforming growth factor β-1 stimulates profibrotic epithelial signaling to activate pericyte-myofibroblast transition in obstructive kidney fibrosis.
- Author
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Wu CF, Chiang WC, Lai CF, Chang FC, Chen YT, Chou YH, Wu TH, Linn GR, Ling H, Wu KD, Tsai TJ, Chen YM, Duffield JS, and Lin SL
- Subjects
- Animals, Cell Cycle Checkpoints physiology, Cell Differentiation physiology, Cells, Cultured, Cytokines biosynthesis, Disease Models, Animal, Disease Progression, Epithelial Cells metabolism, Epithelial-Mesenchymal Transition physiology, Fibrosis, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myofibroblasts pathology, Pericytes metabolism, Pericytes pathology, Signal Transduction physiology, Ureteral Obstruction complications, Ureteral Obstruction pathology, Ureteral Obstruction physiopathology, Kidney pathology, Myofibroblasts physiology, Pericytes physiology, Transforming Growth Factor beta1 physiology
- Abstract
Pericytes have been identified as the major source of precursors of scar-producing myofibroblasts during kidney fibrosis. The underlying mechanisms triggering pericyte-myofibroblast transition are poorly understood. Transforming growth factor β-1 (TGF-β1) is well recognized as a pluripotent cytokine that drives organ fibrosis. We investigated the role of TGF-β1 in inducing profibrotic signaling from epithelial cells to activate pericyte-myofibroblast transition. Increased expression of TGF-β1 was detected predominantly in injured epithelium after unilateral ureteral obstruction, whereas downstream signaling from the TGF-β1 receptor increased in both injured epithelium and pericytes. In mice with ureteral obstruction that were treated with the pan anti-TGF-β antibody (1D11) or TGF-β receptor type I inhibitor (SB431542), kidney pericyte-myofibroblast transition was blunted. The consequence was marked attenuation of fibrosis. In addition, epithelial cell cycle G2/M arrest and production of profibrotic cytokines were both attenuated. Although TGF-β1 alone did not trigger pericyte proliferation in vitro, it robustly induced α smooth muscle actin (α-SMA). In cultured kidney epithelial cells, TGF-β1 stimulated G2/M arrest and production of profibrotic cytokines that had the capacity to stimulate proliferation and transition of pericytes to myofibroblasts. In conclusion, this study identified a novel link between injured epithelium and pericyte-myofibroblast transition through TGF-β1 during kidney fibrosis., (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
4. Novel insights into pericyte-myofibroblast transition and therapeutic targets in renal fibrosis.
- Author
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Chang FC, Chou YH, Chen YT, and Lin SL
- Subjects
- Cell Movement, Endothelial Cells metabolism, Endothelial Cells pathology, Fibrosis metabolism, Fibrosis pathology, Fibrosis therapy, Humans, Kidney metabolism, Macrophage Activation, Myofibroblasts metabolism, Pericytes metabolism, Signal Transduction, Kidney pathology, Kidney Diseases metabolism, Kidney Diseases pathology, Kidney Diseases therapy, Myofibroblasts pathology, Pericytes pathology
- Abstract
Renal fibrosis is a disease affecting millions worldwide and is a harbinger of progressive renal failure. Understanding the mechanisms of renal fibrosis is important for discovering new therapies that are required to prevent loss of renal function. Recently, we identified pericytes that line the kidney microvasculature as the precursor cells of the scar-producing myofibroblasts during kidney injury. Kidney pericytes are extensively branched cells embedded within the capillary basement membrane and stabilize the capillary network through tissue inhibitor of metalloproteinase 3 and angiogenic growth factors. Pericytes detach from endothelial cells and migrate into the interstitial space where they undergo a transition into myofibroblasts after injury. Activation of endothelium, pericyte-myofibroblast transition, and recruitment of inflammatory macrophages lead to capillary rarefaction and fibrosis. Targeting endothelium-pericyte crosstalk by inhibiting vascular endothelial cell growth factor receptors and platelet-derived growth factor receptors in response to injury have been identified as new therapeutic interventions. Furthermore, targeting macrophage activation has also been proven as a novel and safe therapeutic approach for pericyte-myofibroblast transition. However, we are still far from understanding the interaction between pericytes and other cellular elements in normal physiology and during kidney fibrosis. Further studies will be required to translate into more specific therapeutic approaches., (Copyright © 2012. Published by Elsevier B.V.)
- Published
- 2012
- Full Text
- View/download PDF
5. The role played by perivascular cells in kidney interstitial injury.
- Author
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Rojas A, Chang FC, Lin SL, and Duffield JS
- Subjects
- Animals, Capillaries metabolism, Capillaries physiopathology, Cell Communication, Cell Transdifferentiation, Endothelial Cells metabolism, Endothelial Cells pathology, Fibrosis, Humans, Kidney metabolism, Kidney Diseases metabolism, Kidney Diseases physiopathology, Myofibroblasts metabolism, Myofibroblasts pathology, Neovascularization, Physiologic, Pericytes metabolism, Capillaries pathology, Kidney blood supply, Kidney pathology, Kidney Diseases pathology, Pericytes pathology
- Abstract
Fibrosis of the kidney is a disease affecting millions worldwide and is a harbinger of progressive loss of organ function resulting in organ failure. Recent findings suggest that understanding mechanisms of development and progression of fibrosis will lead to new therapies urgently required to counteract loss of organ function. Recently, little-known cells that line the kidney microvasculature, known as pericytes, were identified as the precursor cells which become the scar-forming myofibroblasts. Kidney pericytes are extensively branched cells located in the wall of capillaries, embedded within the microvascular basement membrane, and incompletely envelope endothelial cells with which they establish focal contacts. In response to kidney injuries, pericytes detach from endothelial cells and migrate into the interstitial space where they undergo a transition into myofibroblasts. Detachment leads to fibrosis but also leaves an unstable endothelium, prone to rarefaction. Endothelial-pericyte crosstalk at the vascular endothelial growth factor receptors and platelet derived growth factor receptors in response to injury have been identified as major new targets for therapeutic intervention.
- Published
- 2012
- Full Text
- View/download PDF
6. Targeting endothelium-pericyte cross talk by inhibiting VEGF receptor signaling attenuates kidney microvascular rarefaction and fibrosis.
- Author
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Lin SL, Chang FC, Schrimpf C, Chen YT, Wu CF, Wu VC, Chiang WC, Kuhnert F, Kuo CJ, Chen YM, Wu KD, Tsai TJ, and Duffield JS
- Subjects
- Animals, Capillaries metabolism, Capillaries pathology, Cell Proliferation, Endothelium, Vascular metabolism, Fibrosis, Humans, Immunity, Innate, Kidney metabolism, Mice, Microvessels metabolism, Neovascularization, Pathologic complications, Neovascularization, Pathologic metabolism, Pericytes pathology, Protein Isoforms metabolism, Receptor, Platelet-Derived Growth Factor beta antagonists & inhibitors, Receptor, Platelet-Derived Growth Factor beta metabolism, Vascular Endothelial Growth Factor A metabolism, Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors, Endothelium, Vascular pathology, Kidney blood supply, Kidney pathology, Microvessels pathology, Pericytes metabolism, Signal Transduction, Vascular Endothelial Growth Factor Receptor-2 metabolism
- Abstract
Microvascular pericytes and perivascular fibroblasts have recently been identified as the source of scar-producing myofibroblasts that appear after injury of the kidney. We show that cross talk between pericytes and endothelial cells concomitantly dictates development of fibrosis and loss of microvasculature after injury. When either platelet-derived growth factor receptor (R)-β signaling in pericytes or vascular endothelial growth factor (VEGF)R2 signaling in endothelial cells was blocked by circulating soluble receptor ectodomains, both fibrosis and capillary rarefaction were markedly attenuated during progressive kidney injury. Blockade of either receptor-mediated signaling pathway prevented pericyte differentiation and proliferation, but VEGFR2 blockade also attenuated recruitment of inflammatory macrophages throughout disease progression. Whereas injury down-regulated angiogenic VEGF164, the dys-angiogenic isomers VEGF120 and VEGF188 were up-regulated, suggesting that pericyte-myofibroblast differentiation triggers endothelial loss by a switch in secretion of VEGF isomers. These findings link fibrogenesis inextricably with microvascular rarefaction for the first time, add new significance to fibrogenesis, and identify novel therapeutic targets., (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
7. Angiopoietin 1 influences ischemic reperfusion renal injury via modulating endothelium survival and regeneration
- Author
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Chiang, Wen-Chih, Huang, Yu-Chin, Fu, Ten-I, Chen, Ping-Min, Chang, Fan-Chi, Lai, Chun-Fu, Wu, Vin-Cent, Lin, Shuei-Liong, and Chen, Yung-Ming
- Published
- 2019
- Full Text
- View/download PDF
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